Potential cardiotonic agents. 4. Synthesis, cardiovascular activity, molecular and crystal structure of 5-phenyl- and 4-(4-pyridinyl)-substituted 2(1H)-pyridinethiones

• Published in: Pharmazie Vol. 44; no. 12; p. 809
• Main Authors: Hagen, V, Rumler, A, Reck, G, Hagen, A, Labes, D, Heer, S
• Format: Journal Article
• Language: German
• Published: Germany 01-12-1989
• Subjects: Animals; Blood Pressure - drug effects; Cardiotonic Agents - analysis; Cardiotonic Agents - chemical synthesis; Cardiotonic Agents - pharmacology; Crystallization; Dihydropyridines - chemical synthesis; Dihydropyridines - pharmacology; Dogs; Guinea Pigs; Hemodynamics - drug effects; In Vitro Techniques; Milrinone; Molecular Conformation; Myocardial Contraction - drug effects; Pyridines - chemical synthesis; Pyridines - pharmacology; Pyridones - pharmacology; Structure-Activity Relationship; Thiones - chemical synthesis; Thiones - pharmacology; X-Ray Diffraction
• ISSN: 0031-7144

Cyclisation of the vinylogous amidinium salt 1 or the 4-ethoxy- and 4-morpholino-3-butene-2-ones, respectively, 4 and 6 with cyano-thioacetamide yielded the 5-(4-pyridinyl)-, 6-methyl-5-(4-pyridinyl)- and 6-methyl-5-phenyl-, respectively, substituted 3-cyano-2(1H)-pyridinethiones 3, 5 and 7. The 2(1H)-pyridinethiones 3, 5 and 7a as well as the in 3-position unsubstituted or carbamoyl substituted derivatives 8 and 9 were obtained from the corresponding 2-chloro-pyridines and potassium sulfide, too. Especially compound 5 showed remarkable positive inotropic potency and, additionally, vasodilator activity. The molecular and crystal structure of 5 have been determines by X-ray structure analysis. Based on the molecular structure charge distribution and electrostatic potential were evaluated. The results are discussed in comparison with those of milrinone.